Construction of an artificial phosphoketolase pathway that efficiently catabolizes multiple carbon sources to acetyl-CoA

PLoS Biol. 2023 Sep 21;21(9):e3002285. doi: 10.1371/journal.pbio.3002285. eCollection 2023 Sep.

Abstract

The canonical glycolysis pathway is responsible for converting glucose into 2 molecules of acetyl-coenzyme A (acetyl-CoA) through a cascade of 11 biochemical reactions. Here, we have designed and constructed an artificial phosphoketolase (APK) pathway, which consists of only 3 types of biochemical reactions. The core enzyme in this pathway is phosphoketolase, while phosphatase and isomerase act as auxiliary enzymes. The APK pathway has the potential to achieve a 100% carbon yield to acetyl-CoA from any monosaccharide by integrating a one-carbon condensation reaction. We tested the APK pathway in vitro, demonstrating that it could efficiently catabolize typical C1-C6 carbohydrates to acetyl-CoA with yields ranging from 83% to 95%. Furthermore, we engineered Escherichia coli stain capable of growth utilizing APK pathway when glycerol act as a carbon source. This novel catabolic pathway holds promising route for future biomanufacturing and offering a stoichiometric production platform using multiple carbon sources.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl Coenzyme A
  • Aldehyde-Lyases* / genetics
  • Aldehyde-Lyases* / metabolism
  • Carbon* / metabolism
  • Glucose / metabolism
  • Metabolic Engineering

Substances

  • Acetyl Coenzyme A
  • phosphoketolase
  • Carbon
  • Aldehyde-Lyases
  • Glucose

Grants and funding

This work was supported by National Key R&D Program of China (2018YFA0901600 to YL), National Key R&D Program of China (2021YFC2103500 to YL), Strategic Priority Research Program of the Chinese Academy of Sciences-Precision Seed Design and Breeding (XDA24020103-3 to HJ), Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project (TSBICIP-KJGG-007 to HJ), Tianjin Outstanding Scholar Program (YM), and the National Natural Science Foundation of China (31901015 to XL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.